Transmission event of SARS-CoV-2 delta variant reveals multiple vaccine breakthrough infections
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Abstract
Background
This study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health.
Methods
Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x.
Results
Viral sequencing revealed an infection cluster of 6 vaccinated patients infected with the delta (B.1.617.2) SARS-CoV-2 variant. With no history of vaccine breakthrough, this suggests the delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152.
Conclusions
Delta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with previously described increased transmissibility over alpha variant and now, possible vaccine breakthrough.
Funding
Parts of this work was supported by the National Institute of Allergy and Infectious Diseases (1U19AI144297) and Baylor College of Medicine internal funding.
Article activity feed
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Our take
This study, available as a preprint and thus not yet peer-reviewed, investigated six symptomatic COVID-19 cases in vaccinated individuals after an outdoor wedding in Houston, Texas in April 2021. All patients were infected with the Delta variant, and phylogenetic analysis confirms likely transmission during the wedding event. However, limited data on time since vaccination (or antibody titers) for these patients makes it difficult to confirm how many were true vaccine breakthroughs, and the total number of asymptomatic infections acquired at the wedding is unknown. Breakthrough infections should continue to be monitored, especially as Delta or other new variants increase in frequency. However, it is important to remember that vaccine breakthroughs are to be expected and do not suggest vaccine ineffectiveness; in fact, …
Our take
This study, available as a preprint and thus not yet peer-reviewed, investigated six symptomatic COVID-19 cases in vaccinated individuals after an outdoor wedding in Houston, Texas in April 2021. All patients were infected with the Delta variant, and phylogenetic analysis confirms likely transmission during the wedding event. However, limited data on time since vaccination (or antibody titers) for these patients makes it difficult to confirm how many were true vaccine breakthroughs, and the total number of asymptomatic infections acquired at the wedding is unknown. Breakthrough infections should continue to be monitored, especially as Delta or other new variants increase in frequency. However, it is important to remember that vaccine breakthroughs are to be expected and do not suggest vaccine ineffectiveness; in fact, vaccination may have protected some of these patients (and other wedding guests) from more severe outcomes.
Study design
other
Study population and setting
This study describes SARS-CoV-2 infections acquired at a wedding in Houston, Texas with 92 attendees in April 2021. All wedding activities occurred outside in a large open-air tent, and attendees were required to be fully vaccinated. Two guests (Patients 0a and 0b) travelled from India to attend the wedding and tested positive four days after the wedding. Patient 0b complained of fatigue the first night of the wedding but associated it with jet lab. Patient 0a developed a cough two days after the wedding, and both developed a fever three days after the wedding. They had both received their second dose of the Covaxin BBV152 vaccine 10 days prior to traveling to Texas. Five other guests reported close contact with patients 0a and 0b, and four tested positive for SARS-CoV-2. Two had been vaccinated with the Pfizer vaccine, and two had been vaccinated with the Moderna vaccine, though vaccination dates for these patients were not reported. All six positive patients reported symptoms, and at least two required hospitalizations. Patient 0a was one of those hospitalized, and he died approximately one month after the wedding from complications of COVID-19.
Summary of main findings
Whole genome sequencing revealed that all six cases were caused by the SARS-CoV-2 Delta variant. Phylogenetic analysis revealed that the cases were closely related (viruses formed a distinct cluster within the Delta clade of the phylogenetic tree). The authors characterize all six infections as vaccine breakthroughs due to reported vaccination status of all patients.
Study strengths
In this study, the phylogenetic and epidemiological data both suggest the same conclusion: that transmission of SARS-CoV-2 occurred at a wedding attended by all six patients. The study also provided detailed information on patient demographics and comorbidities, and includes travel history of two patients from India, indicating the likely source of initial infection.
Limitations
The manuscript does not provide any details on testing of other wedding attendees, including those that may have been asymptomatic, limiting our understanding of the true number of attendees that may have been infected. Additionally, the manuscript does not discuss the severity of symptoms in patients other than 0a and 1. Finally, the paper states that Patients 0a and 0b received their second vaccine dose only 10 days prior to travel, which may have not been long enough for them to mount a full immune response. Therefore, only up to four of these cases may have been true vaccine breakthrough infections (though time since vaccination was not reported for the other patients).
Value added
This manuscript presents additional evidence of symptomatic infections — particularly of the Delta variant — in vaccinated individuals.
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SciScore for 10.1101/2021.06.28.21258780: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Protocols for collection, qPCR testing, and whole genome sequencing were approved by the Baylor College of Medicine Institutional Review Board (H-47423). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources The reaction mixes and the thermocycler conditions were performed according to the Swift Normalase® Amplicon Panels (SNAP) Workflow. SNAPsuggested: (SNAP, RRID:SCR_007936)Swift amplicon data analysis: Swift amplicon data were analyzed using Swift Biosciences Sarscov2 analysis pipeline (https://github.com/swiftbiosciences/sarscov2analysis_docker) with minimum read … SciScore for 10.1101/2021.06.28.21258780: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Protocols for collection, qPCR testing, and whole genome sequencing were approved by the Baylor College of Medicine Institutional Review Board (H-47423). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources The reaction mixes and the thermocycler conditions were performed according to the Swift Normalase® Amplicon Panels (SNAP) Workflow. SNAPsuggested: (SNAP, RRID:SCR_007936)Swift amplicon data analysis: Swift amplicon data were analyzed using Swift Biosciences Sarscov2 analysis pipeline (https://github.com/swiftbiosciences/sarscov2analysis_docker) with minimum read coverage depth of 3. Swift Biosciencessuggested: NoneThe GATK variants were next filtered with allele fraction >=80, and min read depth 30x12,13. GATKsuggested: (GATK, RRID:SCR_001876)Global alignment of 334 sequences including the sequences from the current study was done using MAFFT v7.48017. MAFFTsuggested: (MAFFT, RRID:SCR_011811)Maximum-likelihood phylogenetic tree with boot strap (5,000) was generated using IQ-Tree V2.1.218,19. IQ-Treesuggested: (IQ-TREE, RRID:SCR_017254)Annotation and visualization of the tree was carried out by using FigTree v1.4.4 (http://tree.bio.ed.ac.uk/software/figtree/). FigTreesuggested: (FigTree, RRID:SCR_008515)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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